Roche announced positive interim results from the phase III IMAgINATION trial, demonstrating that its investigational treatment sefaxersen significantly reduces proteinuria in adults with primary IgA nephropathy (IgAN) after 37 weeks. The study met its primary endpoint, with patients treated with sefaxersen showing a clinically meaningful reduction in the 24-hour urine protein-to-creatinine ratio (UPCR) compared to placebo. Proteinuria is a key indicator of kidney damage, and its reduction is strongly linked to preserving long-term kidney function. The treatment is administered as a once-monthly subcutaneous injection, enabling self-administration by patients. Roche noted that the safety profile remained consistent with prior data, with no new safety concerns identified.
IgA nephropathy (IgAN), also known as Berger’s disease, is a chronic, progressive autoimmune kidney condition affecting at least 25 adults per million globally. Up to 50% of diagnosed patients progress to end-stage kidney disease within 20 years, often requiring dialysis or transplantation. The disease is characterized by immune complex deposition in the kidneys, activating the alternative complement pathway and leading to inflammation and damage. Current therapies primarily target downstream effects, such as blood pressure control and proteinuria reduction, but have not addressed the underlying immune-mediated mechanisms.
Sefaxersen is an antisense oligonucleotide designed to inhibit complement factor B production in the liver, blocking a key driver of kidney damage in IgAN. By reducing elevated complement factor B levels, sefaxersen lowers urinary protein levels, potentially slowing disease progression. The IMAgINATION study enrolled 459 participants randomized 1:1 to sefaxersen or placebo. The primary endpoint was the change in UPCR from baseline at 37 weeks. The study will continue through week 105 to assess changes in estimated glomerular filtration rate (eGFR), with interim data expected at an upcoming medical congress and shared with health authorities.
Roche’s Chief Medical Officer, Levi Garraway, highlighted the potential of sefaxersen to modify kidney function surrogates, offering a new treatment option to delay dialysis or transplantation. The findings align with updated KDIGO 2025 guidelines, which emphasize the need for therapies targeting both immune-mediated causes and downstream kidney damage. While new treatments have expanded options, unmet needs persist, including improved long-term kidney preservation and more targeted disease-modifying approaches.
Roche licensed sefaxersen from Ionis Pharmaceuticals for complement-mediated diseases. The company has a broader pipeline exploring immune system disorders, including chronic lung disease, inflammatory bowel disease, lupus, autoimmune kidney diseases, and atopic dermatitis. The results mark a step toward addressing the substantial burden of IgAN on patients, families, and healthcare systems.
